Neurostimulation has been applied to modulate various physiologic functions and treat various diseases. For example, cardiovascular functions are modulated by neural signals in portions of the autonomic nervous system. The heart is innervated with sympathetic and parasympathetic nerves. Neural activities in these nerves are known to regulate, among other things, heart rate, blood pressure, and myocardial contractility. Modulation of such neural activities by neurostimulation therefore provides for modulation of such cardiovascular functions. One example is the modulation of cardiac functions in a patient suffering heart failure or myocardial infarction. Electrical stimulation applied to the vagus nerve is known to decrease the heart rate and the contractility, lengthening the systolic phase of a cardiac cycle, and shortening the diastolic phase of the cardiac cycle. Such effects of vagus nerve stimulation allow for control of myocardial remodeling. In addition to treating cardiac disorders such as myocardial remodeling, vagus nerve stimulation is also known to be effective in treating disorders including, but not limited to, depression, anorexia nervosa/eating disorders, pancreatic function, epilepsy, hypertension, inflammatory disease, and diabetes.
However, neurostimulation may decrease its effectiveness in a patient after it has been applied to the patient for a period of time. Such neural accommodation or tolerance may be due to neural reorganization (plasticity) or attenuation of end organ responsiveness. Neural plasticity is the change of structure, function, and organization of neurons in response to new experience. An end organ may decrease its responsiveness to stimulation due to receptor down regulation, reduced sensitivity of receptors, change in second messenger systems, cell signaling cascades, etc. Thus, there is a need for maintaining efficacy of neurostimulation over time, especially when the neurostimulation is applied as a long-term therapy.